Fluoro-substituted N-nitrosamines. 2. Metabolism of N-nitrosodiethylamine and of fluorinated analogs in liver microsomal fractions.

In vitro metabolism of N-nitrosodiethylamine (NDEA) and of its two fluorinated analogs N-nitroso-2,2,2-trifluoroethyl-ethylamine (NDEA-F3) and N-nitroso-bis(2,2,2-trifluoro-ethyl)amine (NDEA-F6) was comparatively investigated using rat liver microsomes and S-9 fraction. Aldehydes, nitrite and unchanged nitrosamines were determined. Additionally the mutagenicity was measured in a Salmonella/mammalian microsome assay. NDEA and NDEA-F3 were deethylated and, to a smaller extent, denitrosated. Dealkylation of NDEA-F3 at the fluorinated ethyl group, however, was strongly inhibited. NDEA-F6 was practically not metabolized under the in vitro conditions used. In contrast to NDEA, the mutagenicity of NDEA-F3 was at best marginal; NDEA-F6 was not mutagenic. The results show that substitution of fluorine in beta-position of NDEA strongly influences alpha-C-hydroxylation and denitrosation.